Analysis of immunoglobulin light chains by gel isoelectric focusing led to the discovery of genetic polymorphism in certain inbred strains of mice. This polymorphism seems to involve distinct groups of light chains and we have proposed that it may be due to differences in the Vk-gene repertoires in inbred mouse strains. The research project will be directed towards the definition of the groups of light chains involved in the polymorphism. Our approach to this problem, already successful in the case of one of the variants, is to screen light chains of large numbers of myelomas generated in different inbred mouse strains. Large numbers of myelomas derived from BALB/c, NZB as well as BALB/c .C58 and BALB/c .AKR -Ly2a3a congenic strains have been made available to us through the generosity of Drs. Michael Potler, NIH, Martin Weigert of ICR, Philadelphia, and Paul Gottlieb of MIT. In the case of the BALB/c and NZB myelomas we have already identified one of the important Vk groups differing (in expression?) in these two strains. We are currently working out complete amino acid sequences on 6 of the BALB/c proteins belonging to this group. So far, the sequence data indicate that we are dealing with a closely related group of kappa chains, namely Vkl. Complete sequencing of several members of this group will give an indication of the extent of diversity that may be found in Vk regions controlled by the Igk-Ef2 locus. The procedure we have elaborated for the analysis of normal light chain profiles may enable direct identification of many kappa chain subgroups simultaneously in a single serum sample. We are now applying the technique to the analysis of the dynamics and genetic control of light chains produced in the response to DNP-carrier conjugates. Results so far indicate that light chains produced in the DNP-response are strongly influenced by loci on chromosome 6 and much less so by the genetic origin of the heavy chain partner.